临床与病理杂志2018，Vol.38Issue(2)：257-266,10.DOI:10.3978/j.issn.2095-6959.2018.02.006
胃肠道间质瘤c-KIT,PDGFRA基因突变及CD117,DOG-1蛋白的表达情况
c-KIT and PDGFRA mutations and expression of CD117 and DOG-1 in gastrointestinal stromal tumors
摘要
Abstract
Objective: To analyze the mutation patterns of c-KIT and PDGFRA in 133 gastrointestinal stromal tumor (GIST) cases and expression of CD117 and DOG-1 in 94 GIST cases. Methods: Next generation sequencing (NGS) and immunohistochemistry (IHC) were used to analyze gene mutations and protein expression in formalin-fixed paraffin-embedded slides and to investigate the association between gene mutation and primary locations. Results: Among 133 GIST cases, 74 were males and 59 were females with the majority over 40 years old. There were 57 cases in the stomach, 59 in the small intestine, 8 in the abdominal cavity, 5 in the rectum, 2 in the mesenterium, and 2 in the pelvic cavity. Overall, c-KIT mutations were identified in 97 cases (72.9％): 79 of them were involved with exon 11 (59.4％), 13 with exon 9 (9.8％), 4 with exon 13 (3.0％), and 5 with exon 17 (3.8％), including 5 cases (3.8％) presented with double mutations. Exon 9 insertion was mainly identified in small intestine, whereas deletion of W557_K558 of exon 11 was common in stomach. Mutation of PDGFRA was present in 11 cases (8.3％), with 8 of them in exon 18 (6.0％), 3 in exon 12 (2.3％). All PDGFRA-mutated cases were derived from stomach. We also investigated the expression of CD117 and DOG-1 in 94 cases: 89 (94.7％) were CD117(+), 92 (97.9％) were DOG-1(+). A total of 88 cases were double positive (74 harboring c-KIT mutation and 4 harboring PDGFRA mutation), 1 case was CD117 single positive (wild-type), 4 cases were DOG-1 single positive (1 c-KIT mutated and 3 PDGFRA mutated), and 1 case was double negative (c-KIT mutated). There was significant correlation between the expression of CD117 and DOG-1 (P＜0.01). Conclusion: The mutation rate of c-KIT and PDGFRA in GIST were high. There were relations between mutation form and primary location of GIST. Most GIST cases showed CD117 and DOG-1 double positive pattern, whereas double negative and CD117 single positive were rare. DOG-1 single positive cases were mainly found in PDGFRA-mutated cases. Gene analysis is essential for diagnosis of GIST in single positive and double negative cases.关键词
胃肠道间质瘤/c-KIT/PDGFRA/CD117/DOG-1Key words
gastrointestinal stromal tumor/c-KIT/PDGFRA/CD117/DOG-1引用本文复制引用
陈净慈,吴焕文,陆俊良,周炜洵,梁智勇..胃肠道间质瘤c-KIT,PDGFRA基因突变及CD117,DOG-1蛋白的表达情况[J].临床与病理杂志,2018,38(2):257-266,10.基金项目
分子病理研究中心创新基金(2016ZX0176-1). This work was supported by the Center for Molecular Pathology, Chinese Academy of Medical Sciences & Peking Union Medical College (2016ZX0176-1). （2016ZX0176-1）
